This grant proposes to study the significance of altered glycoprotein synthesis in tumors. A cancer-associated serum galactosyltransferase isoenzyme (GT-II) has been separated from the normal isoenzyme (GT-I). In addition, a cancer-associated galactosyltransferase acceptor (CAGA), a preferred acceptor of GT-II, was found to be cytotoxic to transformed cells with no apparent effect on non-transformed cells. A specific aim of this research is to purify and characterize these isoenzymes of galactosyltransferase, attempt to produce monospecific antibodies to them, and evaluate their significance to normal differentiations and tumor biology. The other major aim concerns CAGA, its origin, mechanism of cytotoxicity, possible use as a therapeutic agent, and the synthesis or isolation f CAGA-like substances. The studies will utilize material from patients, animal tumor models and tissue culture cells as sources of enzyme and CAGA. The animal tumor models and tissue culture cells will be used to evaluate correlations with tumor growth and study the mechanism of cytotoxicity, particularly its effect on plasmalemma structure and function. The molecular mechanism or release of galactosyltransferases from tumors in animals and cells in tissue culture will be studied. Structural studies, particularly on the oligosaccharide moiety of GT and CAGA will be done and correlated with their biochemical and cellular effects. These studies should better characterize the cancer-associated isoenzyme GT-II which has been proposed as a cancer serum marker. The studies on CAGA may provide new approaches to selectively destroying cancer cells and insights into developing new anti-cancer drugs.